Closing the gap between ¹⁹F and ¹⁸F chemistry.

Area of Science:

• Radiochemistry
• Medicinal Chemistry
• Nuclear Medicine

Background:

• Positron emission tomography (PET) is crucial for drug discovery and medical diagnostics.
• Fluorine-18 (¹⁸F) is a key radionuclide for PET imaging due to its favorable properties.
• Limited methodologies previously hindered the synthesis of ¹⁸F-labeled radiotracers.

Purpose of the Study:

• To review recent breakthroughs in ¹⁸F-radiochemistry, focusing on C-¹⁸F bond formation.
• To highlight advancements enabling late-stage ¹⁸F-incorporation into complex molecules.
• To discuss the impact of these methods on drug discovery and diagnostic applications.

Main Methods:

• Exploration of novel activation modes for ¹⁸F incorporation.
• Application of transition metal catalysis, photoredox catalysis, and organocatalysis.
• Utilization of new ¹⁸F-labeled fluorination reagents and readily available precursors.

Main Results:

• Significant progress in late-stage ¹⁸F-fluorination methodologies.
• Development of processes for incorporating ¹⁸F into complex (bio)molecules without pre-functionalization.
• Emergence of new C-¹⁸F bond-forming reactions.

Conclusions:

• Recent advances have greatly expanded the toolkit for synthesizing ¹⁸F-labeled radiotracers.
• These developments facilitate broader access to PET imaging agents for medicine.
• The field is shifting towards nucleophilic fluoride strategies, impacting broader ¹⁹F-chemistry research.